Malignant brain tumors, glioblastoma multiforme (GBM), are a fatal form of cancer. Despite advances in neurosurgical techniques, chemotherapeutic regimens, and radiotherapy protocols, the median survival following surgical resection and adjuvant therapy is less than 12 months. Glioblastomas have one of the highest rates of angiogenesis among all malignant tumors. The level of angiogenesis in glioblastomas is a direct predictor of patient survival.
However, non-invasive diagnostic/prognostic assessment of the angiogenesis in glioblastomas by imaging techniques is lacking. Similarly, there are no effective anti-angiogenic therapies for glioblastomas. Developing imaging, diagnostic and therapeutic approaches to assess and inhibit angiogenesis in glioblastomas, respectively, depends on the characterization of specific markers of brain tumor angiogenesis that could serve as targets.
Typically, GBM is diagnosed as an area of contrast enhancement on MRI—this technique does not provide useful information on the molecular characteristics of GBM nor about the rate of angiogenesis.
GBM therapy currently includes neurosurgical tumor removal followed by highly toxic radio- and chemo-therapeutic regimens (and several experimental treatments). However the success rate remains low.
The key reason for failure of neurosurgical intervention in curing GBM is cancer recurrence. Recurrence occurs because of the locally invasive nature of the tumor—microscopic regional metastases are not removed during surgery and cause tumor recidive. Failure of chemotherapeutic treatments is due to poor penetration of drugs across the blood-tumor barrier.
Accordingly, it is desirable to develop diagnostic and/or therapeutic formulations that specifically recognize abnormal blood vessels in brain tumors. These formulations could be adapted for use in molecular imaging (optical, MRI, PET) in vivo to diagnose brain tumor and evaluate the extent of angiogenesis and invasion, to prevent growth of abnormal tumor vessels, and/or to target/deliver other therapeutics to tumor vessels to destroy tumor vessels.